Unfolding the Future - The Functional Fold: Amyloid Structures in Nature - page 161

can often be problematic as it is unlikely that access to numerous
techniques will be available at a single location, and thus convincing
identification of amyloid remains a major hurdle in the development
of the field, especially in the case of serendipitous discoveries.
The isolation of fibrils from natural materials is tremendously
challenging, unlike the use of fibrils formed in vitro from com-

11

mercially available peptides. In addition, the extreme structural

stability of functional amyloid makes it difficult to apply conventional
protein science approaches to their purification and characterization.
Special techniques such as preparative gel electrophoresis and
specific solubilization by organic acids are often required. A
disproportionate amount of time can be spent optimizing these
steps, severely delaying the subsequent characterization of amyloid.
However, this characterization is often a crucial step in proving that
the amyloid serves a biological function for the organism, rather
than merely the coincidental presence of amyloid in a sample
of natural material. Due to the breadth of functions identified to
date, it is likely that there are significant structural differences at
the molecular level between fibrils that have been harvested from
different living organisms. However, the challenges of purification
and characterization will need to be overcome before the full extent
of these differences can be explored and understood.

10.3 The Latest Discoveries
Several notable discoveries of functional amyloid have taken
place while this topic has been in the final stages of production.
One recent discovery indicates that a broad family of peptide and
protein hormones in secretory granules of the endocrine system
are stored in the cross-

β

-sheet rich conformation which defines

amyloid. This form serves the biological function of long-term

storage at high concentration within mammalian tissue and, as
indicated from

9

studies, specifically within the human body.
Whilst the finding clearly indicate that functional amyloids in the
pituitary and other organs can contribute to normal cell and tissue
physiology, the function in this case runs contrary to the widespread
notion that amyloid fibrils are very stable and are not thought to
release monomers, which would be a prerequisite upon granule
secretion. To dispute this notion the authors performed an amyloid
release assay for a selection of hormone fibrils showing that all

in vitro